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Abstract There is limited evidence regarding the causal inference of emphysema and functional small airway disease in the subsequent progression of chronic obstructive pulmonary disease (COPD). Patients consisting of two independent cohorts diagnosed with COPD and underwent two serial chest CT scans were included. Total percent emphysema (PRMEmph) and fSAD (PRMfSAD) was quantified via PRM. To investigate the progression of emphysema, we divided COPD patients with PRMEmph

Antibiotic-induced gut microbiota disruption constitutes a major risk factor for Clostridioides difficile infection (CDI). Further, antibiotic therapy, which is the standard treatment option for CDI, exacerbates gut microbiota imbalance, thereby causing high recurrent CDI incidence. Consequently, probiotic-based CDI treatment has emerged as a long-term management and preventive option. However, the mechanisms underlying the therapeutic effects of probiotics for CDI remain uninvestigated, thereby creating a knowledge gap that needs to be addressed. To fill this gap, we used a multiomics approach to holistically investigate the mechanisms underlying the therapeutic effects of probiotics for CDI at a molecular level. We first screened Bifidobacterium longum owing to its inhibitory effect on C. difficile growth, then observed the physiological changes associated with the inhibition of C. difficile growth and toxin production via a multiomics approach. Regarding the mechanism underlying C. difficile growth inhibition, we detected a decrease in intracellular adenosine triphosphate (ATP) synthesis due to B. longum–produced lactate and a subsequent decrease in (deoxy)ribonucleoside triphosphate synthesis. Via the differential regulation of proteins involved in translation and protein quality control, we identified B. longum–induced proteinaceous stress. Finally, we found that B. longum suppressed the toxin production of C. difficile by replenishing proline consumed by it. Overall, the findings of the present study expand our understanding of the mechanisms by which probiotics inhibit C. difficile growth and contribute to the development of live biotherapeutic products based on molecular mechanisms for treating CDI.

Clostridioides difficile is a gram-positive anaerobic bacterium that causes antibiotic-associated infections in the gut. C. difficile infection develops in the intestine of a host with an imbalance of the intestinal microbiota and, in severe cases, can lead to toxic megacolon, intestinal perforation, and even death. Despite its severity and importance, however, the lack of a model to understand host-pathogen interactions and the lack of research results on host cell effects and response mechanisms under C. difficile infection remain limited. Here, we developed an in vitro anaerobic-aerobic C. difficile infection model that enables direct interaction between human gut epithelial cells and C. difficile through the Mimetic Intestinal Host–Microbe Interaction Coculture System. Additionally, an integrative multiomics approach was applied to investigate the biological changes and response mechanisms of host cells caused by C. difficile in the early stage of infection. The C. difficile infection model was validated through the induction of disaggregation of the actin filaments and disruption of the intestinal epithelial barrier as the toxin-mediated phenotypes following infection progression. In addition, an upregulation of stress-induced chaperones and an increase in the ubiquitin proteasomal pathway were identified in response to protein stress that occurred in the early stage of infection, and downregulation of proteins contained in the electron transfer chain and ATP synthase was observed. It has been demonstrated that host cell energy metabolism is inhibited through the glycolysis of Caco-2 cells and the reduction of metabolites belonging to the TCA cycle. Taken together, our C. difficile infection model suggests a new biological response pathway in the host cell induced by C. difficile during the early stage of infection at the molecular level under anaerobic-aerobic conditions. Therefore, this study has the potential to be applied to the development of future therapeutics through basic metabolic studies of C. difficile infection.

Introduction: To enhance photothermal treatment (PTT) efficiency, a delivery method that uses cell vector for nanoparticles (NPs) delivery has drawn attention and studied widely in recent years. Objectives: In this study, we demonstrated the feasibility of M1 activated macrophage as a live vector for delivering NPs and investigated the effect of NPs loaded M1 stimulated by Lipopolysaccharide on PTT efficiency in vivo. Methods: M1 was used as a live vector for delivering NPs and further to investigate the effect of NPs loaded M1 on PTT efficiency. Non-activated macrophage (MФ) was stimulated by lipopolysaccharide (LPS) into M1 and assessed for tumor cell phagocytic capacity towards NPs Results: We found M1 exhibited a 20-fold higher uptake capacity of NPs per cell volume and 2.9-fold more active infiltration into the tumor site, compared with non-activated macrophage MФ. We injected M1 cells peritumorally and observed that these cells penetrated into the tumor mass within 12 h. Then, we conducted PTT using irradiation of a near-infrared laser for 1 min at 1 W/cm2. As a result, we confirmed that using M1 as an active live vector led to a more rapid reduction in tumor size within 1 day indicating that the efficacy of PTT with NPs-loaded M1 is higher than that with NPs-loaded MФ. Conclusion: Our study demonstrated the potential role of M1 as a live vector for enhancing the feasibility of PTT in cancer treatment.

In ideal diffraction-limited optical microscopy imaging depth is limited by the multiply scattered wave. Here, the authors present a space gating method, based on an acoustic focus in the object plane and reconstruction using only the acousto-optically modulated ballistic wave, and demonstrate increased imaging depth in scattering samples.

Faecalibacterium prausnitzii, a major commensal bacterium in the human gut, is well known for its anti-inflammatory effects, which improve host intestinal health. Although several studies have reported that inulin, a well-known prebiotic, increases the abundance of F. prausnitzii in the intestine, the mechanism underlying this effect remains unclear. In this study, we applied liquid chromatography tandem mass spectrometry (LC-MS/MS)-based multiomics approaches to identify biological and enzymatic mechanisms of F. prausnitzii involved in the selective digestion of inulin. First, to determine the preference for dietary carbohydrates, we compared the growth of F. prausnitzii in several carbon sources and observed selective growth in inulin. In addition, an LC-MS/MS-based intracellular proteomic and metabolic profiling was performed to determine the quantitative changes in specific proteins and metabolites of F. prausnitzii when grown on inulin. Interestingly, proteomic analysis revealed that the putative proteins involved in inulin-type fructan utilization by F. prausnitzii, particularly β-fructosidase and amylosucrase were upregulated in the presence of inulin. To investigate the function of these proteins, we overexpressed bfrA and ams, genes encoding β-fructosidase and amylosucrase, respectively, in Escherichia coli, and observed their ability to degrade fructan. In addition, the enzyme activity assay demonstrated that intracellular fructan hydrolases degrade the inulin-type fructans taken up by fructan ATP-binding cassette transporters. Furthermore, we showed that the fructose uptake activity of F. prausnitzii was enhanced by the fructose phosphotransferase system transporter when inulin was used as a carbon source. Intracellular metabolomic analysis indicated that F. prausnitzii could use fructose, the product of inulin-type fructan degradation, as an energy source for inulin utilization. Taken together, this study provided molecular insights regarding the metabolism of F. prauznitzii for inulin, which stimulates the growth and activity of the beneficial bacterium in the intestine.

This study provides empirical evidence of the impact of recentralized governance on environmental performance by examining the implementation of a clean heating transition. It investigated the impact of a centralized clean heating transition on sulfur dioxide (SO2) levels in Shanxi province from January 2015 to March 2021. Using a difference-in-differences approach, this study found that the centralized clean heating transition led to a significant improvement in air quality; however, the excessive response of Shanxi province prevented adequate heating supply for residents. As a result, the Chinese government had to reverse its initial plans for a coal ban and the promotion of gas plants. This outcome implies that recentralization cannot control the autonomy of local governments in responding to and achieving the central targets, even though it may provide incentives to prioritize environmental issues. The recentralization proved to be ineffective, in contrast to what was theoretically anticipated, and even undermined the energy transition efforts.

To effectively mitigate global greenhouse gas emissions, both industrialized and developing countries should participate in the energy transition that to replace fossil fuels with renewable energy. Multilateral development banks (MDBs) have been scaling up their renewable energy finance to developing countries to help them achieve their renewable energy targets. This study examines the evolution of energy financing of the World Bank, the oldest and largest MDB, by reviewing and estimating its sector-specific energy investments made over the last 35 years (1985–2019). The results confirm that the World Bank is on the right track supporting energy transition in developing countries, overall; however, limitations exist. While the share of investments in non-hydro renewable energy (NHRE) in the World Bank’s total energy finance was expanded from 1% (1985–1990) to 16.5% (2011–2019), the share of fossil fuels contracted from 51.8% (1985–1990) to 15.2% (2011–2019). However, commitments to fossil fuels have been sustained, but financing for NHRE—US$1.2 billion per year after the adoption of the Paris Agreement—is still insufficient to meet demand. Moreover, NHRE finance tended to be concentrated in middle-income developing countries. To accelerate the energy transition in developing countries, the World Bank needs to increase NHRE finance with more support for low-income countries while reducing fossil fuel finance.

In this study, Bi0.5Sb1.5Te3.0 (BST) nanoparticles (NPs) with high crystallinities were synthesized via a mechanochemical process (MCP). X-ray diffraction (XRD), and Raman and X-ray photoelectron spectroscopy (XPS) spectra of the BST NPs showed that the Bi, Sb, and Te powders successfully formed BiSbTe phase and transmission electron microscopy (TEM) images, verifying the high crystallinity and smaller size, albeit agglomerated. The as-synthesized BST NPs with agglomerated clusters were ground into smaller sizes of approximately 41.8 nm with uniform distribution through a simple wet-milling process during 7 days. The thermal conduction behaviors of bulk alloys fabricated by spark plasma sintering (SPS) of the BST NPs were studied by comparing those of samples fabricated from as-synthesized BST NPs and a BST ingot. The thermal conductivities (κ) of the BST nanocomposites were significantly reduced by introducing BST NPs with smaller grain sizes and finer distributions in the temperature range from 300 to 500 K. The BST nanocomposites fabricated from wet-milled BST NPs offered ultralow κ values of 0.84 W m−1 K−1 at approximately 398 K.

Triterpenoids echinocystic acid and its glycosides, isolated from several Eclipta prostrata, have been reported to possess various biological activities such as anti-inflammatory, anti-bacterial, and anti-diabetic activity. However, the cytotoxicity of the triterpenoids in human cancer cells and their molecular mechanism of action are poorly understood. In the present study, we found that eclalbasaponin II with one glucose moiety has potent cytotoxicity in three ovarian cancer cells and two endometrial cancer cells compared to an aglycone echinocystic acid and eclalbasaponin I with two glucose moiety. Eclalbasaponin II treatment dose-dependently increased sub G1 population. Annexin V staining revealed that eclalbasaponin II induced apoptosis in SKOV3 and A2780 ovarian cancer cells. In addition, eclalbasaponin II-induced cell death was associated with characteristics of autophagy; an increase in acidic vesicular organelle content and elevation of the levels of LC3-II. Interestingly, autophagy inhibitor BaF1 suppressed the eclalbasaponin II-induced apoptosis. Moreover, eclalbasaponin II activated JNK and p38 signaling and inhibited the mTOR signaling. We further demonstrated that pre-treatment with a JNK and p38 inhibitor and mTOR activator attenuated the eclalbasaponin II-induced autophagy. This suggests that eclalbasaponin II induces apoptotic and autophagic cell death through the regulation of JNK, p38, and mTOR signaling in human ovarian cancer cells.

Nanoparticles (NPs) exposed to a biological milieu will strongly interact with proteins, forming “coronas” on the surfaces of the NPs. The protein coronas (PCs) affect the properties of the NPs and provide a new biological identity to the particles in the biological environment. The characterization of NP-PC complexes has attracted enormous research attention, owing to the crucial effects of the properties of an NP-PC on its interactions with living systems, as well as the diverse applications of NP-PC complexes. The analysis of NP-PC complexes without a well-considered approach will inevitably lead to misunderstandings and inappropriate applications of NPs. This review introduces methods for the characterization of NP-PC complexes and investigates their recent applications in biomedicine. Furthermore, the review evaluates these characterization methods based on comprehensive critical views and provides future perspectives regarding the applications of NP-PC complexes.

Purpose: Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib. Materials and Methods: We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias. Results: Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, p=0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, p=0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank p=0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank p=0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all p>0.05). Conclusion: Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly. [ABSTRACT FROM AUTHOR]

Background/Aims: Increased prevalence of nonalcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) has been reported. However, the effects of NAFLD on the outcome of IBD remains unclear. We investigated whether the presence of NAFLD could influence the outcomes of patients with IBD. Methods: We recruited 3,356 eligible patients with IBD into our study between November 2005 and November 2020. Hepatic steatosis and fibrosis were diagnosed using hepatic steatosis index of ≥30 and fibrosis-4 of ≥1.45, respectively. The primary outcome was clinical relapse, defined based on the following: IBD-related admission, surgery, or first use of corticosteroids, immunomodulators, or biologic agents for IBD. Results: The prevalence of NAFLD in patients with IBD was 16.7%. Patients with hepatic steatosis and advanced fibrosis were older, had a higher body mass index, and were more likely to have diabetes (all p<0.05). Conclusions: Hepatic steatosis was independently associated with increased risks of clinical relapse in patients with ulcerative colitis and Crohn’s disease, whereas fibrotic burden in the liver was not. Future studies should investigate whether assessment and therapeutic intervention for NAFLD will improve the clinical outcomes of patients with IBD. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the quality of surveillance ultrasound (US) for hepatocellular carcinoma (HCC) utilizing fusion imaging. Methods: This research involved a secondary analysis of a prospectively recruited cohort. Under institutional review board approval, participants referred for surveillance US who had undergone liver computed tomography (CT) or magnetic resonance imaging (MRI) within the past year were screened between August 2022 and January 2023. After patient consent was obtained, the US visualization score in the Liver Imaging Reporting and Data System was assessed with fusion imaging at the time of examination. This score was compared to that of conventional US using the extended McNemar test. Multivariable logistic regression analysis was used to identify factors independently associated with a US visualization score of B or C. Factors limiting visualization of focal lesions were recorded during fusion imaging. Results: Among the 105 participants (mean age, 59±11 years; 66 men), US visualization scores of B and C were assigned to 57 (54.3%) and 17 (16.2%) participants, respectively, by conventional US and 54 (51.4%) and 32 (30.5%) participants, respectively, by fusion imaging. The score distribution differed significantly between methods (P=0.010). Male sex was independently associated with US visualization scores of B or C (adjusted odds ratio, 3.73 [95% confidence interval, 1.30 to 10.76]; P=0.015). The most common reason (64.5%) for lesion nondetection was a limited sonic window. Conclusion: Conventional US may underestimate the limitations of the sonic window relative to real-time fusion imaging with pre-acquired CT or MRI in the surveillance of HCC. [ABSTRACT FROM AUTHOR]